The purpose of these studies is to elucidate the mechanisms involved in transmitter release at synapses in the central nervous system. The roles that various neurotransmitters may play in neuronal integration is also being studied. The isolated spinal cord of the frog will continue to be used as an experimental model and further studies will be done on the functional roles of monoamines in the modulation of patterns of activity of spinal motoneurons. We have already shown that 5-hydroxytryptamine is a neurotransmitter at spinal neurons and provides excitatory inputs to motoneurons; now the roles of the catecholamines will be examined. Preliminary data suggest that these provide inhibitory inputs to motoneurons; intracellular and extracellular recordings will be done to establish whether the receptors are alpha-adrenergic and/or Beta-adrenergic. Neuronal activity will be recorded following administration of alpha- and Beta-adrenergic receptor blockers and substances which interfere with their synthesis and breakdown. Emphasis will be placed on the levels of these substances within the cord following these procedures using biochemical analysis. Furthermore, the relationship of these monoamines and functional activity to cyclic nucleotide levels will be examined. Cyclic AMP and GMP is at present being assayed in the spinal cord under control experimental conditions and now it is hoped to correlate changes in electrical activity with changes in monoamine and cyclic nucleotide levels.